As ligands of G protein-coupled receptor GPR34, lipids (e.g., ether phospholipids, phosphonoether lipids, glycerophospholipids, phosphonoglycerolipids, sphingolipids, sphingophospholipids, phosphonosphingolipids, etc.) are reported (WO 03/052414).
It is known that lysophosphatidylserine which is one of glycerophospholipids (hereinafter sometimes referred to as lyso-PS) has the histamine release activity on rat mast cells stimulated by an antigen or concanavalin A (Nature, 279, 250-252, 1979; FEBS Lett., 105, 58-62, 1979), the activity of releasing histamine by synergistically acting on rat mast cells together with nerve growth factor (FEBS Lett., 138, 190-192, 1982), the growth regulating activity on human T cells (FEBS Lett., 316, 1-4, 1993), and the activity of potentiating the differentiation-inducing ability of NGF on PC 12 cells (Neurosci. Lett., 248, 77-80, 1998).
Mast cells cause degranulation by antigenic stimulation after sensitization with an antibody to release chemical mediators such as histamine, leukotriene, serotonin, etc., and are deeply involved in type I hypersensitivity reaction. On the other hand, mast cells secrete various cytokines after antigenic stimulation to affect the functions of T cells and eosinophils and are important as immune regulatory cells.
In late years it is suggested that interleukin-13 (hereinafter IL-13), which is one of cytokines, plays a more important role than IL-4 in the pathology of allergic diseases. IL-13 mRNA is expressed in local areas such as the lichenified lesion of a patient with atopic dermatitis, the airway epithelial cells of a patient with bronchial asthma, the nasal mucosa of a patient with chronic allergic rhinitis, etc. and is considered to relate to IgE production. In bronchial asthma or the like, eosinophils and mast cells are accumulated in respiratory submucosal tissues or epithelial cells. It is thus considered that IL-13 expressed therein may be produced mainly by mast cells, clearly indicating that IL-13 acts directly on bronchial epithelial cells or smooth muscle to cause airway hyperresponsiveness or increased mucus production. Also, IL-13 draws attention as a cause not only for allergic disease but for Hodgkin's disease, ulcerative colitis, pulmonary fibrosis, granuloma, etc.